Molecular characterization of the ldmdr1 multidrug resistance gene from Leishmania donovani

Nancy Hendrickson, C. David Sifri, Debbie M. Henderson, Thomas Allen, Dyann F. Wirth, Buddy Ullman

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The ldmdr1 gene that confers resistance to multiple structurally dissimilar hydrophobic drugs in Leishmania donovani has been isolated within a 5.4-kb Xmal fragment from a genomic library of L. donovani DNA and its protein coding region sequenced. The longest open reading frame within ldmdr1 encodes a 146.5-kDa protein of 1341 amino acids, designated LDMDR1. The primary structure and predicted membrane topology of LDMDR1 indicates that it is a member of the P-glycoprotein superfamily with the greatest homology to the mammalian multidrug resistance P-glycoproteins. A 2.3-kb SalI fragment derived from a second ldmdr1 allele was also cloned from the L. donovani library. Nucleotide sequence analysis of a portion of the SalI insert revealed 5 single base differences from its counterpart within the 5.4-kb XmaI fragment, one of which created a Pvu restriction site polymorphism. Southern blots of PvuI-digested DNA divulged that the amplified ldmdr1 gene copies in a multidrug-resistant L. donovani strain were all derived from the single ldmdr1 allele whose protein coding segment was sequenced in its entirety.

Original languageEnglish (US)
Pages (from-to)53-64
Number of pages12
JournalMolecular and Biochemical Parasitology
Volume60
Issue number1
DOIs
StatePublished - 1993

Fingerprint

MDR Genes
Leishmania donovani
Open Reading Frames
Alleles
P-Glycoproteins
Genomic Library
DNA
Multiple Drug Resistance
P-Glycoprotein
Southern Blotting
Genes
Libraries
Sequence Analysis
Proteins
Amino Acids
Membranes
Pharmaceutical Preparations

Keywords

  • Gene amplification
  • Leishmania donovani
  • Membrane
  • Multidrug resistance
  • P-glycoprotein
  • Transport

ASJC Scopus subject areas

  • Molecular Biology
  • Parasitology

Cite this

Molecular characterization of the ldmdr1 multidrug resistance gene from Leishmania donovani. / Hendrickson, Nancy; Sifri, C. David; Henderson, Debbie M.; Allen, Thomas; Wirth, Dyann F.; Ullman, Buddy.

In: Molecular and Biochemical Parasitology, Vol. 60, No. 1, 1993, p. 53-64.

Research output: Contribution to journalArticle

Hendrickson, Nancy ; Sifri, C. David ; Henderson, Debbie M. ; Allen, Thomas ; Wirth, Dyann F. ; Ullman, Buddy. / Molecular characterization of the ldmdr1 multidrug resistance gene from Leishmania donovani. In: Molecular and Biochemical Parasitology. 1993 ; Vol. 60, No. 1. pp. 53-64.
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